Functional near-infrared spectroscopy in toddlers: Neural differentiation of communicative cues and relation to future language abilities.

The toddler and preschool years are a time of significant development in both expressive and receptive communication abilities. However, little is known about the neurobiological underpinnings of language development during this period, likely due to difficulties acquiring functional neuroimaging data. Functional near-infrared spectroscopy (fNIRS) is a motion-tolerant neuroimaging technique that assesses cortical brain activity and can be used in very young children. Here, we use fNIRS during perception of communicative and noncommunicative speech and gestures in typically developing 2- and 3-year-olds (Study 1, n = 15, n = 12 respectively) and in a sample of 2-year-olds with both fNIRS data collected at age 2 and language outcome data at age 3 (Study 2, n = 18). In Study 1, 2- and 3-year-olds differentiated between communicative and noncommunicative stimuli as well as between speech and gestures in the left lateral frontal region. However, 2-year-olds showed different patterns of activation from 3-year-olds in right medial frontal regions. In Study 2, which included two toddlers identified with early language delays along with 16 typically developing toddlers, neural differentiation of communicative stimuli in the right medial frontal region at age 2 predicted receptive language at age 3. Specifically, after accounting for variance related to verbal ability at age 2, increased neural activation for communicative gestures (vs. both communicative speech and noncommunicative gestures) at age 2 predicted higher receptive language scores at age 3. These results are discussed in the context of the underlying mechanisms of toddler language development and use of fNIRS in prediction of language outcomes.

Systematic Review: Emotion Dysregulation in Syndromic Causes of Intellectual and Developmental Disabilities.

OBJECTIVE: To summarize the current state of the literature regarding emotion dysregulation (ED) in syndromic intellectual disabilities (S-IDs) in 6 of the most common forms of S-IDs-Down syndrome, fragile X syndrome (FXS), tuberous sclerosis complex, Williams syndrome, Prader-Willi syndrome, and Angelman syndrome-and to determine future research directions for identification and treatment of ED. METHOD: PubMed bibliographic database was searched from date of inception to May 2021. PRISMA 2020 guidelines were followed with the flowchart, table of included studies, list of excluded studies, and checklist provided. Filters applied included human research and English. Only original research articles were included in the final set, but review articles were used to identify secondary citations of primary studies. All articles were reviewed for appropriateness by 2 authors and summarized. Inclusion criteria were met by 145 articles (Down syndrome = 29, FXS = 55, tuberous sclerosis complex = 11, Williams syndrome = 18, Prader-Willi syndrome = 24, Angelman syndrome = 8). RESULTS: Each syndrome review was summarized separately and further subdivided into articles related to underlying neurobiology, behaviors associated with ED, assessment, and targeted intervention. FXS had the most thorough research base, followed by Down syndrome and Prader-Willi syndrome, with the other syndromes having more limited available research. Very limited research was available regarding intervention for all disorders except FXS. CONCLUSION: Core underlying characteristics of S-IDs appear to place youth at higher risk for ED, but further research is needed to better assess and treat ED in S-IDs. Future studies should have a standard assessment measure of ED, such as the Emotion Dysregulation Inventory, and explore adapting established curricula for ED from the neurotypical and autism spectrum disorder fields.

Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by core impairments in social communication as well as restricted, repetitive patterns of behavior and/or interests. Individuals with ASD, which includes about 2% of the US population, have challenges with activities of daily living and suffer from comorbid medical and mental health concerns. There are no drugs indicated for the core impairments of ASD. As such, there is a significant need for the development of new medication strategies for individuals with ASD. This first-in-human placebo-controlled, double-blind, crossover study investigated the safety (primary objective) and efficacy of oral SB-121, a combination of L. reuteri, Sephadex® (dextran microparticles), and maltose administered once daily for 28 days in 15 autistic participants. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted. These results provide support for further clinical evaluation of SB-121 as a treatment in autistic patients. To evaluate the safety and tolerability of multiple doses of SB-121 in subjects with autism spectrum disorder. Single-center, randomized, placebo-controlled, double-blind, crossover trial. 15 patients with autism spectrum disorder were randomized and analyzed. Daily dosing of SB-121 or placebo for 28 days, followed by approximately a 14 day washout, then 28 days of dosing with other treatment. Incidence and severity of adverse events, presence of Limosilactobacillus reuteri and Sephadex® in stool, and incidence of bacteremia with positive L. reuteri identification. Additional outcomes include changes from baseline on cognitive and behavior tests as well as biomarker levels. Adverse event rates were similar between SB-121 and placebo, with most reported as mild. There were no severe or serious adverse events. No participants had features of suspected bacteremia or notable changes in vital signs, safety laboratory, or ECG parameters from baseline. There was a statistically significant increase from baseline in the Vineland-3 Adaptive Behavior Composite score (p = 0.03) during SB-121 treatment. There was a trend for increased social/geometric viewing ratio following SB-121 treatment compared to placebo. SB-121 was safe and well tolerated. SB-121-associated directional improvements in adaptive behavior measured by Vineland-3 and social preference as measured with eye tracking were noted.Trial registration: clinicaltrials.gov Identifier: NCT04944901.

Reliability of resting-state electrophysiology in fragile X syndrome.

Objective: Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism spectrum disorder. Currently, there are no established biomarkers for predicting and monitoring drug effects in FXS, and no approved therapies are available. Previous studies have shown electrophysiological changes in the brain using electroencephalography (EEG) in individuals with FXS and animal models. These changes may be influenced by drug therapies. In this study, we aimed to assess the reliability of resting-state EEG measures in individuals with FXS, which could potentially serve as a biomarker for drug discovery. Methods: We collected resting-state EEG data from 35 individuals with FXS participating in placebo-controlled clinical trials (23 males, 12 females; visit age mean+/-std 25.6 +/-8.3). The data were analyzed for various spectral features using intraclass correlation analysis to evaluate test-retest reliability. The intervals between EEG recordings ranged from same-day measurements to up to six weeks apart. Results: Our results showed high reliability for most spectral features, with same-day reliability exceeding 0.8. Features of interest demonstrated ICC values of 0.60 or above at longer intervals. Among the features, alpha band relative power exhibited the highest reliability. Conclusion: These findings indicate that resting-state EEG can provide consistent and reproducible measures of brain activity in individuals with FXS. This supports the potential use of EEG as an objective biomarker for evaluating the effects of new drugs in FXS. Significance: The reliable measurements obtained from power spectrum-based resting-state EEG make it a promising tool for assessing the impact of small molecule drugs in FXS.

An fNIRS Study of Brain Lateralization During Observation and Execution of a Fine Motor Task.

Brain activity in the action observation network (AON) is lateralized during action execution, with greater activation in the contralateral hemisphere to the side of the body used to perform the task. However, it is unknown whether the AON is also lateralized when watching another person perform an action. In this study, we use fNIRS to measure brain activity over the left and right cortex while participants completed actions with their left and right hands and watched an actor complete action with their left and right hands. We show that while activation is lateralized when the participants themselves are moving, brain lateralization is not affected by the side of the body when the participant is observing another person's action. In addition, we demonstrate that individual differences in hand preference and dexterity between the right and left hands are related to brain lateralization patterns.

Sex differences in resting EEG power in Fragile X Syndrome.

Electrophysiological alterations may represent a neural substrate of impaired neurocognitive processes and other phenotypic features in Fragile X Syndrome (FXS). However, the role of biological sex in electroencephalography (EEG) patterns that differentiate FXS from typical development has not been determined. This limits use of EEG in both the search for biomarkers of impairment in FXS as well as application of those markers to enhance our understanding of underlying neural mechanisms to speed treatment discovery. We investigated topographical relative EEG power in participants at rest in a sample of males and females with FXS and in age- and sex-matched typically developing controls (TDC) using a cluster-based analysis. While alterations in theta and low beta power were similar across males and females in FXS, relative power varied by sex in the alpha, upper beta, gamma, and epsilon frequency bands. Follow up analyses showed that Individual Alpha Peak Frequency (IAPF), a continuous variable that may capture atypicalities across the theta and alpha ranges in neurodevelopmental disorders, also varied by sex. Finally, performance on an auditory filtering task correlated with theta power in males, but not females with FXS. The impact of biological sex on resting state EEG power differences in FXS is discussed as it relates to potential GABAergic and glutamatergic etiologies of neurocognitive deficits in FXS.

Audiovisual speech integration and lipreading in autism.

BACKGROUND: During speech perception, the ability to integrate auditory and visual information causes speech to sound louder and be more intelligible, and leads to quicker processing. This integration is important in early language development, and also continues to affect speech comprehension throughout the lifespan. Previous research shows that individuals with autism have difficulty integrating information, especially across multiple sensory domains. METHODS: In the present study, audiovisual speech integration was investigated in 18 adolescents with high-functioning autism and 19 well-matched adolescents with typical development using a speech in noise paradigm. Speech reception thresholds were calculated for auditory only and audiovisual matched speech, and lipreading ability was measured. RESULTS: Compared to individuals with typical development, individuals with autism showed less benefit from the addition of visual information in audiovisual speech perception. We also found that individuals with autism were significantly worse than those in the comparison group at lipreading. Hierarchical regression demonstrated that group differences in the audiovisual condition, while influenced by auditory perception and especially by lipreading, were also attributable to a unique factor, which may reflect a specific deficit in audiovisual integration. CONCLUSIONS: Combined deficits in audiovisual speech integration and lipreading in individuals with autism are likely to contribute to ongoing difficulties in speech comprehension, and may also be related to delays in early language development.